March 24, 2018

expert reaction to literature review on thyroid hormone-disrupting chemicals in pregnancy and brain development disorders in children

A new literature review, published in Endocrine Connections, explores recent findings on the main categories of thyroid hormone disrupting chemicals and their effects on brain development.

Dr Max Davie, Royal College of Paediatrics and Child Health’s Assistant Officer for Health Promotion, and Consultant Community Paediatrician, said:

“The authors attempt to make the case that exposure to a variety of substances has led to the recent increase in ADHD and autism spectrum disorder (ASD) prevalence, and decrease in population IQ. There are a number of reasons to doubt their conclusions.

“The first is that the substances covered vary massively in levels and timing of environmental release – some, such as DDT, have been banned for decades, while others such as perchlorate are naturally occurring as well as man-made. There is no consistent argument made for a causation at any particular time period.

“The second – the case that the environmental levels of these substances exist sufficient for them to enter the food chain at dangerous levels is not made, and having been intensively investigated by environmental agencies in Europe and the US is not considered a threat to human health.

“And thirdly, there probably has not been an increase in the prevalence of ASD or ADHD in the last few decades, but instead an increase in identification and diagnosis. Also, by most measures population IQ has been increasing over the past decades.”

Prof Ieuan Hughes, Society for Endocrinology member, and Emeritus Professor of Paediatrics, University of Cambridge, said:

“This is a review paper, not an original paper, which draws on literature suggesting that endocrine disrupting chemicals can interfere with thyroid hormone production and action, which may be relevant in the developing foetus, infant and child. The authors quite rightly emphasise the importance of normal thyroid function for brain development in foetal and early child development. This was the reason for developing the newborn screening programme for congenital hypothyroidism, almost 40 years ago, in order to start thyroid hormone treatment as soon as possible after birth. Such intervention has been highly successful in preventing adverse neurodevelopment in children born with an abnormal thyroid.

“So what is the evidence that numerous chemicals in the environment can interfere with endocrine function (including thyroid function), which is of relevance to human development? Not much, simply because at best, the evidence is based on associations from epidemiological studies in humans and more direct evidence only in animal studies. Indeed, the authors quote their own work to show endocrine disrupting chemicals found in human amniotic fluid can interfere with the development of the embryo……of the frog!

“This review covers all the usual endocrine disrupting chemicals researched in greater detail in reproductive endocrinology (such as pesticides, BPA, DDT, brominated flame retardants) and then tries to extrapolate the findings by proposing such exposure may explain an apparent increase in neurodevelopmental disorders, such as attention deficit hyperactivity disorder and autistic spectrum conditions. To extrapolate so widely to such conditions that still pose challenges for diagnosis, accurate information on prevalence and abundant theories on causation, is disingenuous. While this is a useful review on the literature relating to the possible effects of endocrine disrupting chemicals on thyroid function, it does not provide novel insights in the field from the perspective of original data.”

“It is important to understand how the environment affects brain development, but to do that we need high-quality research. This low-quality review presents a series of inconclusive studies in an unscientific manner. Based on this poor evidence it is impossible to agree with the view proposed by the research team.

“There is some excellent autism research going on around the world, but poor quality research like this is not fit to be shared with the public. I would encourage all researchers to take a more robust approach to their studies and a more responsible approach to communicating their findings. Autistic people and their family members deserve better.”

“This is paper is a subjective review of the literature of environmental chemicals and their potential impact on thyroid function and neurodevelopment. Overall the paper provides a sound overview of the literature linking environmental contaminants with thyroid dysfunction. However, this paper is only a review of previously published studies and so offers little in the way of new insights. This is a literature review, not a systematic review, so doesn’t provide any new data.

“Moreover, the review fails to provide a critical review of the literature and omits crucial information needed to justify the concluding sentence of the paper. I don’t agree that the evidence presented highlights ‘the current impact of EDC exposure on neurodevelopment’ and argues for ‘rapid public health intervention’ – the evidence just does not support this.

“Specifically, no information is provided on study quality or on the criteria for either including or excluding epidemiological studies in the review, so we can’t know whether all relevant studies were included.

“No information is included on the strengths of the reported associations in the epidemiological studies the review looked at. Many studies on this topic frequently explore the association between the adverse outcome of interest and exposure to multiple chemicals. So, it is important to provide insight into what other chemicals were also included in the epidemiological studies cited and how the authors managed issues of making lots of statistical comparisons and perhaps finding some associations by chance (false positives).

“While including experimental animal data and mechanistic study results in this review is appreciated, the authors have not provided any information on the doses or the length of exposure to chemicals in the studies they include. So it’s hard to determine the relevance of the findings to human health.

“Consequently, this review is a useful paper for someone entering the field of study or others seeking a summary of the literature linking environmental contaminants and thyroid dysfunction, but it should not be cause for concern. The studies described provide a good justification for further research in this area but, because of the significant limitations of this paper, it does not justify the conclusion that the impact of the chemicals discussed in this review on neurodevelopment ‘argue for rapid public health intervention’.”

Dr Michelle Bellingham, Society for Endocrinology member, and lecturer at the University of Glasgow, said:

“The review serves to give an update on the current state of the literature on chemicals that are proposed to have thyroid-disrupting properties. While such reviews are helpful to combine observations from related studies in one place, and identify urgent avenues for future research focus, they must be interpreted with caution.

“The review draws mostly on epidemiological human data and animal experimental data where for both it is difficult to drawn firm conclusions on the effects of chemicals. For human epidemiological studies, it is inherently difficult to be able to infer any more than a strong correlation between one variable (X) and another (Y), and any relationship between them does not mean that we can say for certain that, ‘X exposure causes Y effect’. For example, for the human studies reviewed here, the authors mention studies where exposure to certain chemicals are ‘linked’ or ‘associated’ with increased risk for autism and ADHD in children. Just because there may be an association, does not allow firm conclusions to be made that such chemicals ‘cause’ or are even involved in such disorders.

“For animal experimental studies we should always use caution when extrapolating to effects in humans, not least because humans are not exposed to one chemical, but a mixture of chemicals, which the authors rightly state could alter the way in which a chemical may act alone. This remains a challenge for interpreting these kinds of studies.

“In addition, the review covers experimental studies on several classes of chemicals that are no longer in production, yet for which human exposure is unavoidable. Their presence in human tissues (pregnant women or children) again does not confirm an effect.

“The authors do not present a clear hypothesis for how these may be linked, and until such time as science is able to fully explain such links, we must interpret them with caution. The authors rightly point out that “the lack of full endocrine profiles in these [human] epidemiological studies make it hard to pinpoint the exact mechanism, linking endocrine disruption and neurodevelopmental outcome”, if indeed there is one, and this should be the take home message from this review. The authors rightly conclude that more urgent research is required in this area.”